Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults
ABSTRACT AdCLD-CoV19-1, a chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, was previously reported to elicit robust antibody responses in mice and non-human primates after a single dose. In this study, we conducted a systems serology analysis to investi...
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American Society for Microbiology
2025-01-01
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| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00998-24 |
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| author | Jung Hyuk Lee Yuna Shin Kwang-Soo Shin Ju Yeon Park Mi Sun Kim Young-Shin Park Wuhyun Kim Joon Young Song Ji Yun Noh Hee Jin Cheong Chang-Yuil Kang Sang Hwan Seo Jae-Ouk Kim Deok Ryun Kim Nathaniel S. Hwang Jae Seung Yang Jerome H. Kim Byoung-Shik Shim Manki Song |
| author_facet | Jung Hyuk Lee Yuna Shin Kwang-Soo Shin Ju Yeon Park Mi Sun Kim Young-Shin Park Wuhyun Kim Joon Young Song Ji Yun Noh Hee Jin Cheong Chang-Yuil Kang Sang Hwan Seo Jae-Ouk Kim Deok Ryun Kim Nathaniel S. Hwang Jae Seung Yang Jerome H. Kim Byoung-Shik Shim Manki Song |
| author_sort | Jung Hyuk Lee |
| collection | DOAJ |
| description | ABSTRACT AdCLD-CoV19-1, a chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, was previously reported to elicit robust antibody responses in mice and non-human primates after a single dose. In this study, we conducted a systems serology analysis to investigate changes in humoral immune responses induced by varying doses of the AdCLD-CoV19-1 vaccine in a phase I clinical trial. Serum samples from participants receiving either a low or a high dose of the vaccine were analyzed for antibody features against prototype SARS-CoV-2 spike (S) domains (full-length S, S1, S2, and receptor binding domain), as well as Fc receptor binding and effector functions. While both low- and high-dose vaccines induced robust humoral immune responses following vaccination, the quality of antibody features differed between the dose groups. Notably, while no significant difference was observed between the groups in the induction of most S1-specific antibody features, the high-dose group exhibited higher levels of antibodies and a stronger Fc receptor binding response specific to the S2 antigen. Moreover, univariate and multivariate analyses revealed that the high-dose vaccine induced higher levels of S2-specific antibodies binding to FcγR2A and FcγR3B, closely associated with antibody-dependent neutrophil phagocytosis (ADNP). Further analysis using the Omicron BA.2 variant demonstrated that the high-dose group maintained significantly higher levels of IgG and FcγR3B binding to the S2 antigen and exhibited a significantly higher ADNP response for the S2 antigen compared with the low-dose group. These findings underscore the importance of considering diverse humoral immune responses when evaluating vaccine efficacy and provide insights for optimizing adenovirus vector-based SARS-CoV-2 vaccine doses.IMPORTANCEOptimization of vaccine dose is crucial for eliciting effective immune responses. In addition to neutralizing antibodies, non-neutralizing antibodies that mediate Fc-dependent effector functions play a key role in protection against various infectious diseases, including coronavirus disease 2019. Using a systems serology approach, we demonstrated significant dose-dependent differences in the humoral immune responses induced by the AdCLD-CoV19-1 chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, particularly against the SARS-CoV-2 spike 2 domain. These findings highlight the importance of assessing not only neutralizing antibody titers but also the quality and functionality of antibody responses when evaluating vaccine efficacy. |
| format | Article |
| id | doaj-art-e077d014fbfe43a6981085542055b281 |
| institution | Kabale University |
| issn | 2379-5042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj-art-e077d014fbfe43a6981085542055b2812025-01-28T14:00:56ZengAmerican Society for MicrobiologymSphere2379-50422025-01-0110110.1128/msphere.00998-24Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adultsJung Hyuk Lee0Yuna Shin1Kwang-Soo Shin2Ju Yeon Park3Mi Sun Kim4Young-Shin Park5Wuhyun Kim6Joon Young Song7Ji Yun Noh8Hee Jin Cheong9Chang-Yuil Kang10Sang Hwan Seo11Jae-Ouk Kim12Deok Ryun Kim13Nathaniel S. Hwang14Jae Seung Yang15Jerome H. Kim16Byoung-Shik Shim17Manki Song18International Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaResearch & Development Center, Cellid Co. Ltd., Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaResearch & Development Center, Cellid Co. Ltd., Seoul, South KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, South KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, South KoreaDivision of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, South KoreaResearch & Development Center, Cellid Co. Ltd., Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaSchool of Chemical and Biological Engineering, Seoul National University, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaInternational Vaccine Institute, Seoul, South KoreaABSTRACT AdCLD-CoV19-1, a chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, was previously reported to elicit robust antibody responses in mice and non-human primates after a single dose. In this study, we conducted a systems serology analysis to investigate changes in humoral immune responses induced by varying doses of the AdCLD-CoV19-1 vaccine in a phase I clinical trial. Serum samples from participants receiving either a low or a high dose of the vaccine were analyzed for antibody features against prototype SARS-CoV-2 spike (S) domains (full-length S, S1, S2, and receptor binding domain), as well as Fc receptor binding and effector functions. While both low- and high-dose vaccines induced robust humoral immune responses following vaccination, the quality of antibody features differed between the dose groups. Notably, while no significant difference was observed between the groups in the induction of most S1-specific antibody features, the high-dose group exhibited higher levels of antibodies and a stronger Fc receptor binding response specific to the S2 antigen. Moreover, univariate and multivariate analyses revealed that the high-dose vaccine induced higher levels of S2-specific antibodies binding to FcγR2A and FcγR3B, closely associated with antibody-dependent neutrophil phagocytosis (ADNP). Further analysis using the Omicron BA.2 variant demonstrated that the high-dose group maintained significantly higher levels of IgG and FcγR3B binding to the S2 antigen and exhibited a significantly higher ADNP response for the S2 antigen compared with the low-dose group. These findings underscore the importance of considering diverse humoral immune responses when evaluating vaccine efficacy and provide insights for optimizing adenovirus vector-based SARS-CoV-2 vaccine doses.IMPORTANCEOptimization of vaccine dose is crucial for eliciting effective immune responses. In addition to neutralizing antibodies, non-neutralizing antibodies that mediate Fc-dependent effector functions play a key role in protection against various infectious diseases, including coronavirus disease 2019. Using a systems serology approach, we demonstrated significant dose-dependent differences in the humoral immune responses induced by the AdCLD-CoV19-1 chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, particularly against the SARS-CoV-2 spike 2 domain. These findings highlight the importance of assessing not only neutralizing antibody titers but also the quality and functionality of antibody responses when evaluating vaccine efficacy.https://journals.asm.org/doi/10.1128/msphere.00998-24systems serologySARS-CoV-2adenovirus vector-based vaccineeffector functionspike protein |
| spellingShingle | Jung Hyuk Lee Yuna Shin Kwang-Soo Shin Ju Yeon Park Mi Sun Kim Young-Shin Park Wuhyun Kim Joon Young Song Ji Yun Noh Hee Jin Cheong Chang-Yuil Kang Sang Hwan Seo Jae-Ouk Kim Deok Ryun Kim Nathaniel S. Hwang Jae Seung Yang Jerome H. Kim Byoung-Shik Shim Manki Song Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults mSphere systems serology SARS-CoV-2 adenovirus vector-based vaccine effector function spike protein |
| title | Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults |
| title_full | Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults |
| title_fullStr | Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults |
| title_full_unstemmed | Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults |
| title_short | Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults |
| title_sort | dose dependent serological profiling of adcld cov19 1 vaccine in adults |
| topic | systems serology SARS-CoV-2 adenovirus vector-based vaccine effector function spike protein |
| url | https://journals.asm.org/doi/10.1128/msphere.00998-24 |
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